Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 2-14 have an effective filing date of 08MAY2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/08/2023 & 07/19/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 07/03/2026, Applicant elected, with traverse:
Group I, claims 2-6, and 11-12
Species
SEQ ID NOs: 63, 64, 65 & 66, 67, 112
Human and native
A Chimeric antibody
IgG1
A detection label comprising a luminescent substance
Eukaryotic cell that is a mammalian cell CHO cell
Antibody drug conjugate
The traversal is on the grounds that “the DLL3 binding molecule or the antigen binding fragment thereof as defined by SEQ ID NOs: 63, 64, 65, 66, 6, and 112, the claims of Groups I-IV can share the same or corresponding technical feature therebetween, namely the specific CDR sequences of the elected antibody.”
This argument is not found persuasive, because Group I, contained different species of a DLL3 binding molecule for the treatment of a disease. MPEP 806.04(e) states, “The scope of a claim may be limited to a single disclosed embodiment (i.e., a single species, and thus be designated a specific species claim).” As such, the technical feature that links the Groups is the administration of a DLL3 binding molecule, as indicated in the Requirement for Restriction/Election, is taught by Wesche et al. As such the Requirement is deemed appropriate and is made FINAL.
Status of Claims
Claims 2-14 are currently pending and presented for examination on the merits.
Claim 1 is canceled.
Claims 3-11 are amended.
Claims 7-10, and 13-14 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Regarding claims 2-6 and 11, the term “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 12 is included in this rejection, because it depends from claim 11 but does not cure the deficiencies of claim 11 with respect to 35 U.S.C. 112(b).
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2-6, and 11-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
One of ordinary skill in the art would recognize that the specificity of an antibody is dependent upon the 6 CDR regions and different combinations of CDR sequences greatly alter antigen binding. Regarding the elected species, the instant specification discloses a DLL3 binding molecule comprising the following six CDRs: SEQ ID Nos: 63, 64, 65, 66, 67, and 112. However, the specification does not adequately disclose, for example, a genus of antibodies comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 32.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences, 1982, 79:1979-1983). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
MacCallum et al. (Journal of Molecular Biology, 1996, 262:732-745) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominates, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column).
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site is underscored by Casset et al. (Biochemical and Biophysical Research Communications, 2003, 307:198-205), which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, other CDRs play an important role in the recognition process (page 199, left column) and this is demonstrated in this work by using all CDRs except CDR L2 and additionally using a framework residue located just before the CDR H3 (see page 202, left column). Holm et al. (Molecular Immunology, 2007:1075-1084) describes the mapping of an anti-cytokeratin antibody and found that in addition to the involvement of the residues in the CDR3 of the heavy chain in antigen binding, a residue in CDR2 of the light chain was also involved (abstract). Chen et al. (Journal of Molecular Biology, 1999, 293:865-881) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). There is insufficient evidence or nexus that would lead the skilled artisan to predict the ability of a DLL3 binding molecule comprising fewer than 6 CDR regions of a DLL3 binding molecule known to bind DLL3.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2, 3, 5, 6, 11, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 15, 16, 19, 20, and 31 of copending Application No. 18/836,818 ('818) (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other, because both sets of claims recite: a) a DLL3 binding molecule comprising SEQ ID NOs: 63, 64, 65, 66, 67, & 112 (claim 2), b) comprising an Fc region (claim 3), c) coupling the DLL3 with another biologically active molecule (claim 5), d) a nucleic acid and host eukaryotic cell (claim 6), & e) a pharmaceutical composition (claims 11 and 12).
A comparison of instant SEQ ID NOs: 63, 64, 65 and SEQ ID NO: 11 of ‘818 is shown below.
Instant SEQ ID NOs: 63, 64, 65 and SEQ ID NO: 11 of ‘818.
Query Match 87.3%; Score 168.4; Length 122;
Best Local Similarity 43.2%;
Matches 35; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 SYWIT--------------DIYPGSGSTTNYNEKFKS----------------------- 23
||||| ||||||||||||||||||
Db 31 SYWITWVRQAPGQGLEWMGDIYPGSGSTTNYNEKFKSRVTMTRDTSTSTVYMELSSLRSE 90
Qy 24 ---------ETTVGGAYAMDY 35
||||||||||||
Db 91 DTAVYYCARETTVGGAYAMDY 111
A comparison of instant SEQ ID NOs: 66, 67, 112 and SEQ ID NO: 12 of ‘818 is shown below.
Instant SEQ ID NOs: 66, 67, 112 and SEQ ID NO: 12 of ‘818.
Query Match 82.4%; Score 115.3; Length 107;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASQSINNNLH---------------YVSQSIS--------------------------- 18
||||||||||| |||||||
Db 24 RASQSINNNLHWYQQKPGQAPRLLIKYVSQSISGIPARFSGSGSGTDFTLTISSLEPEDF 83
Qy 19 -----QQTNAWPLT 27
|||||||||
Db 84 AVYYCQQTNAWPLT 97
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 4 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over 13, 15, 16, 19, 20, and 31 of copending Application No. 18/836,818 ('818), as applied to claims 2, 3, 5, 6, 11, and 12, and further in view of Ward et al. (US PG PUB 2016/0229920, publication date: 08/11/2016).
At [0023], Ward e al. teach “methods of detecting and/or visualizing and/or diagnosing the presence of a cancer cell or tissue. The method typically involves contacting a cell or tissue with a bispecific or polyspecific antibody as described herein attached to a detectable label; and detecting the label where detection of the label in association with the cell or tissue indicates the presence of a cell or tissue expressing (including overexpressing) HER3 and/or HER2.”
Based upon these teachings, one of ordinary skill in the art would appreciate that bispecific molecules specific for a tumor antigen may be tethered to a detectable label and used to diagnose cancers that express said tumor antigen. As such one of ordinary skill in the art would have been motivated to modify the bispecific molecule of the conflicting claims to recite conjugation with a detectable label, because the resultant bispecific antibody could be used in the diagnosis of DLL3-expressing diseases.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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